Parp-14 Promotes Survival Of Mammalian Alpha But Not Beta Pancreatic Cells Following Cytokine Treatment

PARP-14 (poly-ADP Ribose Polymerase-14), a member of the PARP family, belongs to the group of Bal proteins (B Aggressive Lymphoma). PARP-14 has recently appeared to be involved in the transduction pathway mediated by JNKs (c Jun N terminal Kinases), among which JNK2 promotes cancer cell survival. Several pharmacological PARP inhibitors are currently used as antitumor agents, even though they have also proved to be effective in many inflammatory diseases. Cytokine release from immune system cells characterizes many autoimmune inflammatory disorders, including type I diabetes, in which the inflammatory state causes beta cell loss. Nevertheless, growing evidence supports a concomitant implication of glucagon secreting alpha cells in type I diabetes progression. Here, we provide evidence on the activation of a survival pathway, mediated by PARP-14, in pancreatic alpha cells, following treatment of alpha TC1.6 glucagonoma and beta TC1 insulinoma cell lines with a cytokine cocktail: interleukin 1 beta (IL-1 beta) interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha). Through qPCR, western blot and confocal analysis, we demonstrated higher expression levels of PARP-14 in alpha TC1.6 cells with respect to beta TC1 cells under inflammatory stimuli. By cytofluorimetric and caspase-3 assays, we showed the higher resistance of alpha cells compared to beta cells to apoptosis induced by cytokines. Furthermore, the ability of PJ-34 to modulate the expression of the proteins involved in the survival pathway suggests a protective role of PARP-14. These data shed light on a poorly characterized function of PARP-14 in alpha TC1.6 cells in inflammatory contexts, widening the potential pharmacological applications of PARP inhibitors.